Twists & Turns in a March for the Cure

The march of anti-Alzheimer drug candidates continues: aducanumab, an anti-amyloid antibody, is awaiting a ruling by the FDA (due by June), after having been rejected in the past and following a recent strong recommendation against approval by the expert panel convened to review the data. Donanemab, another anti-amyloid antibody, in Phase II showed no improvement in patients and did not prevent decline, but did show a slowing of decline by about one-third, which was hailed as a major success by its pharmaceutical company (as Garry Trudeau noted in Doonesbury recently, most pharmacists recommend the products they sell … ). Galantamine, a cholinesterase inhibitor similar to donepezil, reduced the risk for progression to severe dementia but did not stop the cognitive decline.

There is an old African proverb: “If you want to go fast, go alone; if you want to go far, go together.” That is excellent advice in many cases, but what happens when you do go together, and you do indeed go very far — but it is in the wrong direction? Perhaps you end up developing monotherapy after monotherapy after monotherapy, none of which has an optimal effect to reverse cognitive decline sustainably? Perhaps you are on a Gadarene march instead of a march toward a cure?

Result after result supports the concept that, in order to effect sustained cognitive improvement, we must identify the various contributors and target these with a comprehensive, personalized approach. We are all learning more about what the critical contributors are, what techniques must be improved, and how to achieve optimal and sustainable outcomes. We are all making progress — now this is a march worth taking together.